ArticleNature medicine2013
Common noncoding UMOD gene variants induce salt-sensitive hypertension and kidney damage by increasing uromodulin expression.
Article in Nature medicine, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to 3 registered trials, which are not on this map. Cited by 217 papers, 6 of them syntheses that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Role of Genetic Determinants in the Response to Acute Saline Load Testing in Patients With Essential Hypertension (Naload)
Hypertension in High School Students: Genetic and Environmental Factors
The Effect of Dietary Sodium Intake on Ambulatory Blood Pressure Levels According to Urinary Uromodulin Levels in Patients With Chronic Kidney Disease
Who cites it
217 citing papers in PubMed, 6 syntheses or guidelines pooled it, 368 citations in OpenAlex.
- Trans-ethnic kidney function association study reveals putative causal genes and effects on kidney-specific disease aetiologies.Nature communications · 2019Pooled it
- 1000 Genomes-based meta-analysis identifies 10 novel loci for kidney function.Scientific reports · 2017Pooled it
- Genetic associations at 53 loci highlight cell types and biological pathways relevant for kidney function.Nature communications · 2016Pooled it
- Renal Mechanisms of Association between Fibroblast Growth Factor 1 and Blood Pressure.Journal of the American Society of Nephrology : JASN · 2015Pooled it
- Autosomal dominant tubulointerstitial kidney disease: diagnosis, classification, and management--A KDIGO consensus report.Kidney international · 2015Guideline
- Genome-wide association study of kidney function decline in individuals of European descent.Kidney international · 2015Pooled it
- Effect of empagliflozin on circulating proteomics in heart failure: mechanistic insights into the EMPEROR programme.European heart journal · 2022Trial
- The Relationship Between Urine Uromodulin and Blood Pressure Changes: The DASH-Sodium Trial.American journal of hypertension · 2021Trial
- Review
- UMOD Genotype and Clinical Outcomes in Heart Failure Patients Treated with Loop Diuretics: A UK Biobank Pharmacogenetic Cohort Study.Clinical pharmacology and therapeutics · 2026Article
- Salt and chronic kidney disease.Nature reviews. Nephrology · 2026Review
- Uromodulin T62P variant causes kidney tubular stress and injury modulated by age and polygenic risk.medRxiv : the preprint server for health sciences · 2026Article
- Molecular systems, human noncoding sequence variants, and blood pressure.Physiological reviews · 2026Review
- Interplay between uromodulin excretion and water balance in the general adult population.Physiological reports · 2026Article
- A case of ADTKD-UMOD presenting with focal segmental glomerulosclerosis in a young male with a positive family history.BMC nephrology · 2026Article
- Loop Diuretic Dose Intensification versus Adjuvant Thiazide for Diuretic Resistance in Acute Heart Failure: Mechanistic Randomized Controlled Trial.Journal of the American Society of Nephrology : JASN · 2026Article
- Imaging-based organ-specific aging clock predicts human diseases and mortality.NPJ digital medicine · 2026Article
- Recent advances in the clinical significance and physiological functions of uromodulin: a narrative review.BMC nephrology · 2026Review
- Fifty Shades of Risk: Population Studies and the Genetic Architecture of Kidney Diseases.Journal of the American Society of Nephrology : JASN · 2026Review
- Refining the Composition and Significance of Human Kidney Intratubular Casts Using Spatial Protein Imaging.Clinical journal of the American Society of Nephrology : CJASN · 2026Article
157 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
19 authors at 6 institutions in 4 countries.
Funding
Abstract
Hypertension and chronic kidney disease (CKD) are complex traits representing major global health problems. Multiple genome-wide association studies have identified common variants in the promoter of the UMOD gene, which encodes uromodulin, the major protein secreted in normal urine, that cause independent susceptibility to CKD and hypertension. Despite compelling genetic evidence for the association between UMOD risk variants and disease susceptibility in the general population, the underlying biological mechanism is not understood. Here, we demonstrate that UMOD risk variants increased UMOD expression in vitro and in vivo. Uromodulin overexpression in transgenic mice led to salt-sensitive hypertension and to the presence of age-dependent renal lesions similar to those observed in elderly individuals homozygous for UMOD promoter risk variants. The link between uromodulin and hypertension is due to activation of the renal sodium cotransporter NKCC2. We demonstrated the relevance of this mechanism in humans by showing that pharmacological inhibition of NKCC2 was more effective in lowering blood pressure in hypertensive patients who are homozygous for UMOD promoter risk variants than in other hypertensive patients. Our findings link genetic susceptibility to hypertension and CKD to the level of uromodulin expression and uromodulin's effect on salt reabsorption in the kidney. These findings point to uromodulin as a therapeutic target for lowering blood pressure and preserving renal function.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.